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Sendide is a selective and extremely potent antagonist of neurokinin-1 (NK1) receptors in the mouse spinal cord. The antinociceptive activities of sendide, an antagonist of NK1 receptors, and its analogue, [D-Trp7]sendide have been examined after intrathecal (i.t.) administrations in the mouse paw formalin test. Intrathecal administration of sendide (in pmol) reduced both the early and late phases of the formalin-induced licking response. [D-Trp7]sendide also produced a significant antinociceptive response with less potent activity than sendide. Even highest doses (4000 pmol sendide and 8000 pmol [D-Trp7]sendide) examined, there was no motor paralysis of the hindlimbs. Intrathecal morphine inhibited both the early and late phases of the formalin-induced licking response in a dose-dependent manner. The results indicate that the antinociceptive effects of sendide and [D-Trp7]sendide may be mediated at NK1 receptors in the formalin-induced nociception.

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